PURPOSE: Neurexins are neuronal adhesion molecules located in the presynaptic terminal, where they interact with postsynaptic neuroligins to form a transsynaptic complex required for efficient neurotransmission in the brain. Recently, deletions and point mutations of the neurexin 1 (NRXN1) gene have been associated with a broad spectrum of neuropsychiatric disorders. This study aimed to investigate if NRXN1 deletions also increase the risk of idiopathic generalized epilepsies (IGEs). METHODS: We screened for deletions involving the NRXN1 gene in 1,569 patients with IGE and 6,201 controls using high-density oligonucleotide microarrays. KEY FINDINGS: We identified exon-disrupting deletions of NRXN1 in 5 of 1,569 patients with IGE and 2 of 6,201 control individuals (p = 0.0049; odds ratio (OR) 9.91, 95% confidence interval (CI) 1.92-51.12). A complex familial segregation pattern in the IGE families was observed, suggesting that heterozygous NRXN1 deletions are susceptibility variants. Intriguingly, we identified a second large copy number variant in three of five index patients, supporting an involvement of heterogeneous susceptibility alleles in the etiology of IGE. SIGNIFICANCE: We conclude that exon-disrupting deletions of NRXN1 represent a genetic risk factor in the genetically complex predisposition of common IGE syndromes.
|Titolo:||Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy|
|Autori interni:||VIGNOLI, AGLAIA|
|Parole Chiave:||Adult ; Age of Onset ; Anticonvulsants ; Case-Control Studies ; Cell Adhesion Molecules, Neuronal ; DNA Copy Number Variations ; Electroencephalography ; Epilepsy, Generalized ; Exons ; Family ; Female ; Fructose ; Gene Deletion ; Genotype ; Humans; Infant ; Male ; Microarray Analysis ; Middle Aged ; Nerve Tissue Proteins ; Neuropsychological Tests ; Odds Ratio ; Pedigree ; Triazines ; Valproic Acid|
|Settore Scientifico Disciplinare:||Settore MED/39 - Neuropsichiatria Infantile|
Settore MED/03 - Genetica Medica
Settore MED/26 - Neurologia
|Data di pubblicazione:||feb-2013|
|Digital Object Identifier (DOI):||10.1111/epi.12078|
|Appare nelle tipologie:||01 - Articolo su periodico|
File in questo prodotto:
- PubMed Central loading...